This project is aimed at learning about the pathogenesis of immune-mediated eye diseases, mainly by investigating the animal disease, "experimental auto-immune uveitis" (EAU), which is induced in various animals by immunization with certain eye components. EAU is considered a model for certain human ocular conditions. Research during FY 1986 has focused on EAU induced by interphoto-receptor retinoid-binding protein (IRBP). Our previous study (FY-1985) showed that IRBP is highly uveitogenic in Lewis rats. Major new findings include: (1) Rats of different inbred strains vary in their susceptibility to EAU induced by IRBP or by another retinal protein, S-antigen (S-Ag). This finding shows that the susceptibility to EAU is related to genetic makeup and supports the assumption that the susceptibility to immune-mediated diseases in man is also genetically regulated. (2) The pathogenic mechanism of IRBP-induced EAU was found to be cell mediated: the disease could be adoptively transferred by lymphocytes and a correlation was found between EAU development and cellular immunity but not with antibody production. (3) Monkey IRBP was found to be 20 times less uveitogenic in rats than bovine IRBP. The two IRBPs showed cross reactivity when used for stimulation of lymphocytes for EAU induction, but did not cross react by the lymphocyte proliferation assay. This finding indicates that lymphocyte responses in vitro do not necessarily represent their capacity to induce disease in vivo. (4) Monkeys were found highly susceptible to IRBP-induced EAU. This monkey disease is of special interest by showing a close similarity to certain ocular diseases in man, in particular sympathetic ophthalmia and Vogt-Koyanagi-Harada disease. Similarly to these human diseases, IRBP-induced in monkey was expressed mainly as granulomatous choroiditis. In addition to providing a useful model for the human diseases, the findings with IRBP-induced EAU in monkeys support the notion that autoimmune processes to retinal antigens participate in the etiology of certain human eye diseases.